AB0298 SAFETY OF THE JAK INHIBITORS IN COMPARISON WITH THE TNF INHIBITORS IN RHEUMATOID ARTHRITIS: REAL WORLD DATA FROM THE HONG KONG BIOLOGICS REGISTRY
Authors: C. C. Mok, H. So, C. Ho
Journal: Annals of the Rheumatic Diseases (2023)

<h3>Background</h3> The recent Oral Surveillance study has raised concerns about major cardiovascular events and malignancies related to tofacitinib in older rheumatoid arthritis (RA) patients with cardiovascular risk factors. <h3>Objectives</h3> To compare the incidence of major adverse cardiovascular events (MACEs), cancer and infective complications in RA patients using the JAK (JAKis) and TNF inhibitors (TNFis). <h3>Methods</h3> A retrospective analyses of data retrieved from the Hong Kong Biologics Registry from 2008 to 2021 were performed. Patients with RA (fulfilling the EULAR/ACR criteria) who had ever been treated with the JAK or TNF inhibitors were included. Withdrawal rates due to inefficacy or serious adverse events (SAEs) were compared between the two groups, along with the incidence of MACEs, cancer, infective complications and all-cause mortality. The hazard ratios (HRs) of these outcomes were calculated for the JAKis with reference to the TNFis and adjusted for confounding factors in regression models. <h3>Results</h3> A total of 2471 courses of JAKis (n=551) and TNFis (N=1920) were used in 1732 RA patients (83.7% women, age 53.8±12.5 years; follow-up 6431 patient-years). The most frequent JAKi and TNFi prescribed were tofacitinib (81%) and etanercept (37%). Users of the JAKis, compared to the TNFis, had significantly longer RA duration, older age and were more likely to have atherosclerotic risk factors (diabetes mellitus, hypertension, hyperlipidemia, previous coronary heart disease) and a past history of malignancy. The withdrawal rate of the JAKis was significantly lower than the TNFis due to clinical inefficacy or occurrence of SAEs (p&lt;0.001 by survival analyses). A total of 15 and 40 MACEs developed in the JAKi and TNFi group of patients, respectively (incidence 1.34 vs 0.75 per 100 patient-years; p=0.22, adjusted for age, sex and follow-up duration). Moreover, there was no significant difference in the incidence of new cancers between the two groups (0.81 [JAKi] vs 0.85 [TNFi] per 100 patient-years; p=0.25). The adjusted HRs of MACE and cancer in the JAKi users were 1.36[0.62-2.96] (p=0.44) and 0.87[0.39-1.95] (p=0.74), respectively. Rates of infections were significantly higher in the JAKi than TNFi users (16.3 vs 9.9 per 100 patient-years; p=0.02), particularly herpes zoster (3.49 vs 0.94 per 100 patient-years; p&lt;0.001) reactivation. The incidence of tuberculosis infection was similar between the two groups (0.45 [JAKi] vs 0.60 [TNFi]; p=0.21). All-cause mortality occurred in 8 patients in the JAKi group and 25 in the TNFi group and the difference was not statistically significant (0.72 vs 0.47 per 100 patient-years; p=0.54). <h3>Conclusion</h3> In a real-life setting, the JAKis have a better retention rate than the TNFis in patients with RA. There is no increase in the incidence of MACEs, cancers and all-cause mortality observed with the JAKis in comparison to the TNFis, adjusted for age, sex and other confounding factors. However, infective complications, particularly herpes zoster, are more common in the JAKi users. <h3>Acknowledgements</h3> Drs. Cheuk Wan Yim, Chi Hung To, Weng Nga Lao, Stella Pui Yan Wong, Hoi Yan Ng, Jolly Man Yee Lee, Patrick Man Leung Lee, Shirley King Yee Ying, Moon Ho Leung (who contributed to data collection) <h3>Disclosure of Interests</h3> chi chiu mok Speakers bureau: one-off speaker honorarium from Pfizer during the APLAR 2022 meeting, Ho So: None declared, Carmen Ho: None declared.